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Expression of AHR in whole cell lysates from HSC-3 and Cal27 cells was determined by Western immunoblot analysis, using AhR-specific (1:1000, 13790#, Cell signaling), and β-actin-specific (1:2000, A5441, Sigma-Aldrich) antibodies. Cell lysates from three different experiments were prepared and tested.

A) Representative images of HSC-3 cell migration at 24 hours after cells were cultured to confluence, scratched, and treated with vehicle, 10 μM B(a)P, 1 μM PYO, particulate matter 2.5 um (PM2.5), 10 μM B(a)P and 1 μM PYO, or 10 μM B(a)P and PM2.5. Data are representative of 3 independent experiments. Vertical black lines indicate the borders of the original scratch at zero hours. B) SCC2 cells were treated as in "A" and percent exposed area was quantified. Data from 3 experiments were normalized to results obtained with naïve cells and presented as mean percent exposed area + standard error. Asterisks indicate a significant decrease in exposed area, *p

ObjectivesPain and other physical symptoms commonly co-occur in childhood. There is debate about the relevance of somatization in understanding pain. The present review critically appraised and synthesized the extant literature on the relationship between pediatric pain and somatization.MethodsA systematic review (PROSPERO registration #95956) was conducted in Medline, PsycINFO, EMBASE, and CINAHL using search terms related to pain and somatization in children and adolescents. A total of 156 articles were eligible for inclusion in the review. For studies that measured somatization using a symptom questionnaire, descriptions of “somatization” were extracted. Data regarding the relationship between pain and somatization were extracted for studies measuring somatization using a diagnostic category (e.g., Somatic Symptom and Related Disorders [SSRDs]).ResultsWhile many studies using somatic symptom questionnaires described somatization as having a psychological component, this was not always captured in measurement tools. Pain was reported as a common symptom in patients with an SSRD diagnosis, though rates varied depending on the specific diagnosis and pain location. Rates of SSRD diagnoses among pain patients were less frequent than rates of pain amongst SSRD patients.ConclusionsSSRDs and pain commonly co-occur, though rates differ depending on diagnosis and pain location. Understanding the relationship between pain and somatization is complicated by the discrepancy between how somatization is defined and measured in questionnaire studies. A comprehensive and measurable definition of somatization is needed so researchers can better identify the shared and unique contributions of pain and somatization in pediatric populations.

The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of targeted therapeutics. Here, ligand shape-based virtual modeling techniques were used to identify novel AHR ligands on the basis of previously identified chemotypes. Four structurally unique compounds were identified. One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (CB7993113), was further tested for its ability to block three AHR-dependent biologic activities: triple-negative breast cancer cell invasion or migration in vitro and AHR ligand-induced bone marrow toxicity in vivo. CB7993113 directly bound both murine and human AHR and inhibited polycyclic aromatic hydrocarbon (PAH)- and TCDD-induced reporter activity by 75% and 90% respectively. A novel homology model, comprehensive agonist and inhibitor titration experiments, and AHR localization studies were consistent with competitive antagonism and blockade of nuclear translocation as the primary mechanism of action. CB7993113 (IC50 3.3 × 10(-7) M) effectively reduced invasion of human breast cancer cells in three-dimensional cultures and blocked tumor cell migration in two-dimensional cultures without significantly affecting cell viability or proliferation. Finally, CB7993113 effectively inhibited the bone marrow ablative effects of 7,12-dimethylbenz[a]anthracene in vivo, demonstrating drug absorption and tissue distribution leading to pharmacological efficacy. These experiments suggest that AHR antagonists such as CB7993113 may represent a new class of targeted therapeutics for immunomodulation and/or cancer therapy.

The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER-/PR-/Her2- breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER-/PR-/Her2- cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness.

Over 45,000 new cases of oral and pharyngeal cancers are diagnosed and account for over 8,000 deaths a year in the United States. An environmental chemical receptor, the aryl hydrocarbon receptor (AhR), has previously been implicated in oral squamous cell carcinoma (OSCC) initiation as well as in normal tissue-specific stem cell self-renewal. These previous studies inspired the hypothesis that the AhR plays a role in both the acquisition and progression of OSCC, as well as in the formation and maintenance of cancer stem-like cells. To test this hypothesis, AhR activity in two oral squamous cell lines was modulated with AhR prototypic, environmental and bacterial AhR ligands, AhR-specific inhibitors, and phenotypic, genomic and functional characteristics were evaluated. The data demonstrate that: (i) primary OSCC tissue expresses elevated levels of nuclear AhR as compared with normal tissue, (ii) AhR mRNA expression is upregulated in 320 primary OSCCs, (iii) AhR hyperactivation with several ligands, including environmental and bacterial ligands, significantly increases AhR activity, ALDH1 activity, and accelerates cell migration, (iv) AhR inhibition blocks the rapid migration of OSCC cells and reduces cell chemoresistance, (v) AhR knockdown inhibits tumorsphere formation in low adherence conditions, and (vi) AhR knockdown inhibits tumor growth and increases overall survival in vivo. These data demonstrate that the AhR plays an important role in development and progression of OSCC, and specifically cancer stem-like cells. Prototypic, environmental, and bacterial AhR ligands may exacerbate OSCC by enhancing expression of these properties. Implications: This study, for the first time, demonstrates the ability of diverse AhR ligands to regulate AhR activity in oral squamous cell carcinoma cells, as well as regulate several important characteristics of oral cancer stem cells, in vivo and in vitro. Mol Cancer Res; 14(8); 696–706. ©2016 AACR.

Background Self-renewing, chemoresistant breast cancer stem cells are believed to contribute significantly to cancer invasion, migration and patient relapse. Therefore, the identification of signaling pathways that regulate the acquisition of stem-like qualities is an important step towards understanding why patients relapse and towards development of novel therapeutics that specifically target cancer stem cell vulnerabilities. Recent studies identified a role for the aryl hydrocarbon receptor (AHR), an environmental carcinogen receptor implicated in cancer initiation, in normal tissue-specific stem cell self-renewal. These studies inspired the hypothesis that the AHR plays a role in the acquisition of cancer stem cell-like qualities. Results To test this hypothesis, AHR activity in Hs578T triple negative and SUM149 inflammatory breast cancer cells were modulated with AHR ligands, shRNA or AHR-specific inhibitors, and phenotypic, genomic and functional stem cell-associated characteristics were evaluated. The data demonstrate that (1) ALDHhigh cells express elevated levels of Ahr and Cyp1b1 and Cyp1a1, AHR-driven genes, (2) AHR knockdown reduces ALDH activity by 80 %, (3) AHR hyper-activation with several ligands, including environmental ligands, significantly increases ALDH1 activity, expression of stem cell- and invasion/migration-associated genes, and accelerates cell migration, (4) a significant correlation between Ahr or Cyp1b1 expression (as a surrogate marker for AHR activity) and expression of stem cell- and invasion/migration-associated gene sets is seen with genomic data obtained from 79 human breast cancer cell lines and over 1,850 primary human breast cancers, (5) the AHR interacts directly with Sox2, a master regulator of self-renewal; AHR ligands increase this interaction and nuclear SOX2 translocation, (6) AHR knockdown inhibits tumorsphere formation in low adherence conditions, (7) AHR inhibition blocks the rapid migration of ALDHhigh cells and reduces ALDHhigh cell chemoresistance, (8) ALDHhigh cells are highly efficient at initiating tumors in orthotopic xenografts, and (9) AHR knockdown inhibits tumor initiation and reduces tumor Aldh1a1, Sox2, and Cyp1b1 expression in vivo. Conclusions These data suggest that the AHR plays an important role in development of cells with cancer stem cell-like qualities and that environmental AHR ligands may exacerbate breast cancer by enhancing expression of these properties. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0240-y) contains supplementary material, which is available to authorized users.

Recently there has been a great deal of interest in the use of biomaterials to stimulate wound healing. This is largely due to their ability to centralize high concentrations of compounds known to promote wound healing at a needed location. Joints present a unique challenge to using scaffolds because of the presence of enzymes in synovial fluid which are known to degrade materials that would be stable in other parts of the body. The hypothesis of this study was that atelocollagen scaffolds would have greater resistance to enzymatic degradation than scaffolds made of gelatin, fibrin and whole blood. To test this hypothesis, collagen and fibrin-based scaffolds were placed in matrix metallopeptidase-1 (MMP-1), elastase, and plasmin solutions at physiologic concentrations, and the degradation of each scaffold was measured at varying time points. The atelocollagen scaffolds had a significantly greater resistance to degradation by MMP-1, elastase and plasmin over the fibrin based scaffolds. The results suggest that atelocollagen-based scaffolds may provide some protection against premature degradation by synovial fluid enzymes over fibrin-based matrices.

C P J / R P C • M A R C H / A P R I L 2 0 1 1 • V O L 1 4 4 , N O 2 Introduction Although chiropractors often practise independently, there is evidence that a growing number are being integrated into multidisciplinary care environments. Co-management, openness to discussion and patient interest have been found to be key factors for developing a chiropractor’s involvement within a collaborative care setting. With the introduction of Bill 179 in Ontario, pharmacists will potentially be able to extend their scope of practice to improve their focus on clinical care activities. The Ontario Government is investing in collaborative care as a means of optimizing access to a wide range of health professionals to make best use of limited resources in the delivery of primary and specialty health care. In an effort to ensure that chiropractors in Ontario are practising to their full potential, a scope of practice review has been recommended by the chiropractic profession. This case report provides an example of the overlap of scopes of practice between pharmacists and chiropractors, emerging as a new common ally group in patient care. Both the pharmacist and chiropractor have been co-located within a family health team (FHT) environment for more than 5 years. Case history A 25-year-old female was referred by her family physician to a chiropractor for nonpharmacological treatment options regarding pregnancy-related low back pain (PLBP). The patient had a history of knee joint pain, flat feet, asthma, iron deficiency and gastroesophageal reflux disease. At the time of presentation, the medication regimen included: • Pulmicort Turbuhaler 200 mcg, one puff twice a day • Bricanyl Turbuhaler 0.5 mg, one puff every 6 hours, as needed • Ferrous fumarate 300 mg, one capsule daily • Diclectin 2 tablets at bedtime, 1 tablet in the morning and 1 tablet at noon • Acetaminophen 325 mg, 1–2 tablets every 6 hours for pain, as needed The patient was self-medicating with the acetaminophen 325 mg for PLBP, with minimal benefit. The patient presented with progressively worsening neck, middle and low back pain. These symptoms were limiting her ability to work. The chiropractor initiated care that included spinal manipulation, education on posture, muscle techniques and pacing strategies and pregnancyspecific exercises. Chiropractors and pharmacists in a family health team: Unlikely allies in the collaborative management of pregnancy-related low back pain

The effect of prosthesis-patient mismatch on long-term survival after mitral valve replacement (MVR) has received limited attention. This study was performed to determine the predictors of mortality after MVR and influence of prosthesis-patient mismatch on survival.Contemporary mechanical prostheses and bioprostheses were implanted in 2,440 patients with MVR between 1982 and 2002. The mean age was 63.9 +/- 12.1 years and the mean follow-up was 6.1 +/- 4.6 years, a total of 14,797.7 years of follow-up. Prosthesis-patient mismatch was classified by effective orifice area index categories: normal, greater than 1.2 cm(2)/m(2) (345, 14.2%); mild-to-moderate, equal to or less than 1.2 to greater than 0.9 cm(2)/m(2) (1,696, 69.5%); and severe, equal to or less than 0.9 cm(2)/m(2) (399, 16.4%).The predictors of overall mortality were age, age categorization, New York Heart Association III-IV, concomitant coronary artery bypass, ventricular dysfunction, prosthesis type, body mass index, and pulmonary hypertension. All categories of effective orifice area indices (EOAIs) were not predictive of overall mortality, late mortality, or early mortality. The 15-year survival was not differentiated by EOAI categories; 32.0 +/- 4.4%, 32.9 +/- 2.1%, and 36.6 +/- 6.3%, respectively, for the three categories. Pulmonary hypertension influenced mortality by EOAI categories; normal versus mild-to-moderate (p = 0.0317) and normal versus severe (p = 0.0320). The EOAI was not an independent predictor of mortality in the consideration of patients with pulmonary hypertension but there is an interaction between pulmonary hypertension and mild-to-moderate (p = 0.023) and severe (p = 0.031) EOAI.Prosthesis-patient mismatch is not a predictor of overall mortality to 15 years after MVR regardless of the category of effective orifice area index. The preoperative variable, pulmonary hypertension, influences overall mortality in the presence of mild-to-moderate and severe prosthesis-patient mismatch in the survival analysis.

Response biases are systematic biases in responding to test items that are unrelated to the content of the items. Examples often reported in young children include choosing only the lowest or highest anchors of a scale, or choosing a left-to-right sequence of responses. We investigated the presence of response biases in young children's ratings of pain in hypothetical situations, as a way of gauging their developing understanding of a pain scale over the preschool years. Children aged 3-5 years (N=185) rated items from the Charleston Pediatric Pain Pictures (CPPP) using the Faces Pain Scale-Revised (FPS-R). Response biases were identified objectively by computer pattern identification. Anchor biases (choosing the lowest and highest pain faces) occurred in 16% of children. Left-right or right-left sequences occurred in 35%. Monte Carlo simulation established that such patterns occur infrequently by chance (

Recurrent pains are a complex set of conditions that cause great discomfort and impairment in children and adults. The objectives of this study were to (a) describe the frequency of headache, stomachache, and backache in a representative Canadian adolescent sample and (b) determine whether a set of psychosocial factors, including background factors (i.e., sex, pubertal status, parent chronic pain), external events (i.e., injury, illness/hospitalization, stressful-life events), and emotional factors (i.e., anxiety/depression, self-esteem) were predictive of these types of recurrent pain. Statistics Canada's National Longitudinal Survey of Children and Youth was used to assess a cohort of 2488 10- to 11-year-old adolescents up to five times, every 2 years. Results showed that, across 12-19 years of age, weekly or more frequent rates ranged from 26.1%-31.8% for headache, 13.5-22.2% for stomachache, and 17.6-25.8% for backache. Chi-square tests indicated that girls had higher rates of pain than boys for all types of pain, at all time points. Structural equation modeling using latent growth curves showed that sex and anxiety/depression at age 10-11 years was predictive of the start- and end-point intercepts (i.e., trajectories that indicated high levels of pain across time) and/or slopes (i.e., trajectories of pain that increased over time) for all three types of pain. Although there were also other factors that predicted only certain pain types or certain trajectory types, overall the results of this study suggest that adolescent recurrent pain is very common and that psychosocial factors can predict trajectories of recurrent pain over time across adolescence.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that increases the expression of detoxifying enzymes upon ligand stimulation. Recent studies now suggest that novel endogenous roles of the AHR exist throughout development. In an effort to create an optimized model system for the study of AHR signaling in several cellular lineages, we have employed a CRISPR/CAS9 genome editing strategy in induced pluripotent stem cells (iPSCs) to incorporate a reporter cassette at the transcription start site of one of its canonical targets, cytochrome P450 1A1 (CYP1A1). This cell line faithfully reports onCYP1A1expression, with luciferase levels as its functional readout, when treated with an endogenous AHR ligand (FICZ) at escalating doses. iPSC-derived fibroblast-like cells respond to acute exposure to environmental and endogenous AHR ligands, and iPSC-derived hepatocytes increaseCYP1A1in a similar manner to primary hepatocytes. This cell line is an important innovation that can be used to map AHR activity in discrete cellular subsets throughout developmental ontogeny. As further endogenous ligands are proposed, this line can be used to screen for safety and efficacy and can report on the ability of small molecules to regulate critical cellular processes by modulating the activity of the AHR.

Accurate pain assessment is the foundation for effective pain management in children. At present, there is no clear consensus regarding the age at which young children are able to appropriately use self-report scales for pain. This study examined young children's ability to use the Faces Pain Scale-Revised; (FPS-R; [Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain 2001; 93: 173-83]) for pain in response to vignettes and investigated the role of developmental factors in predicting their ability to use the scale. One hundred and twelve healthy children (3-6 years old) were assessed for their ability to accurately use a common faces scale to rate pain in hypothetical vignettes depicting pain scenarios common in childhood. Accuracy was determined by considering whether children's judgements of pain severity matched the pain severity depicted in the various vignettes. Children were also administered measures of numerical reasoning, language, and overall cognitive development. Results indicated that 5- and 6-year-old children were significantly more accurate in their use of the FPS-R in response to the vignettes than 4-year-old children, who in turn were significantly more accurate than 3-year-old children. However, over half of the 6-year-olds demonstrated difficulties using the FPS-R in response to the vignettes. Child age was the only significant predictor of children's ability to use the scale in response to the vignettes. Thus, a substantial number of young children experienced difficulties using the FPS-R when rating pain in hypothetical vignettes, although the ability to use the scale did improve with age.

The World Health Organization has recently added Interprofessional Education (IPE) to its global health agenda recognizing it as a necessary component of all health professionals' education. We suggest mandatory interprofessional shadowing experiences as a mechanism to be used by chiropractic institutions to address this agenda. IPE initiatives of other professions (pharmacy and medicine) are described along with chiropractic. This relative comparison of professions local to our jurisdiction in Ontario, Canada is made so that the chiropractic profession may take note that they are behind other health care providers in implementing IPE. Interprofessional shadowing experiences would likely take place in a multi-disciplinary clinical setting. We offer an example of how two separate professions within a Family Health Team (FHT) can work together in such a setting to enhance both student learning and patient care. For adult learners, using interprofessional shadowing experiences with learner-derived and active objectives across diverse health professional groups may help to improve the educational experience. Mandatory interprofessional shadowing experiences for chiropractors during their training can enhance future collaborative practice and provide success in reaching a goal common to each profession - improved patient care.

The findings of this single-center experience with the Medtronic Mosaic porcine bioprosthesis were evaluated to determine the clinical performance of the valve.Between 1994 and 2000, a total of 657 patients was implanted with the prosthesis. Aortic valve replacement (AVR) was performed in 415 patients (mean age 70.5+/-10.7 years; range: 26-89 years) and mitral valve replacement (MVR) in 242 patients (mean age 70.5+/-9.5 years; range: 19-86 years). Concomitant coronary artery bypass (CAB) was performed in 51.1% and 46.7% of AVR and MVR patients, respectively. The majority of patients were aged over 70 years (59.8% AVR, 58.7% MVR).Survival at six years was 73.0+/-2.4% after AVR, and 74.0+/-5% after MVR (p = NS). Actual freedom from valve-related mortality at six years was 98+/-1% for AVR and 96+/-1% for MVR; freedom from overall thromboembolism (TE) was 86+/-3% for AVR and 89+/-2% for MVR. After AVR, 42 thromboembolic events occurred in 39 patients (23 minor; 14 major; three reversible ischemic neurologic deficits (RIND); two thrombosis). After AVR, the late TE rate was 2.1% per pt-yr, and the major rate 0.6% per pt-yr (exclusive of thrombosis). The overall TE rate after AVR was 2.9% per pt-yr (major rate 1% per pt-yr). After MVR, 25 events occurred in 24 patients (10 minor; eight major; five RIND; two thrombosis). After MVR, the late TE rate was 2.6% per pt-yr, and the major rate 0.7% per pt-yr (exclusive of thrombosis). The overall TE rate after MVR was 3.5% per pt-yr (major rate 1.1% per pt-yr). There were four cases of structural valve deterioration (SVD) (two each after AVR and MVR). Reoperation was performed in three of four cases of thrombosis, and in two of four cases of SVD.The Medtronic Mosaic porcine bioprosthesis is safe and effective. The rate of SVD after six years was low, being zero in the aortic position of patients aged60 years, and zero also in the mitral position of patients aged60 years. The incidence of early and late thromboembolism was contributed to by the advanced age of the patient population.

Objective Experience with the Carpentier-Edwards supra-annular porcine bioprosthesis (Edwards Lifesciences, Irvine, Calif) has been evaluated longitudinally over 20 years. Clinical performance was evaluated by actuarial and actual analysis. Hemodynamic performance was evaluated by echocardiographic/Doppler assessment. Morphology of structural failure was evaluated from pathologic examinations. Methods From 1981 through 1999, 1823 patients (mean age, 68.9 ± 10.9 years; range, 19-89 years) underwent 1847 procedures. Concomitant coronary artery bypass was performed in 788 (42.7%) patients. Previous valve procedures were performed in 107 (5.8%) patients, and other cardiac procedures were performed in 87 (4.7%) patients. Results The overall valve-related complication rate was 4.36% per patient-year (630 patients), with a fatality rate of 0.96% per patient-year (139 patients). Patient survival at 18 years was 15.8% ± 1.6%. Overall late mortality rate was 6.3% per patient-year. Overall actual cumulative freedom at 18 years from reoperation was 85.0% ± 1.2%, valve-related mortality was 88.7% ± 1.1%, and valve-related residual morbidity was 96.3% ± 5.0%. Actual freedom from structural valve deterioration at 18 years was 86.4% ± 1.2% overall, 90.5% ± 1.8% for age 61 to 70 years, and 98.2% ± 0.6% for age greater than 70 years. Structural valve deterioration presented with pathologic evidence consistent with stenosis in 27.6% and insufficiency in 72.4%. Hemodynamic performance at 1 year revealed normal effective orifice area indexes for sizes 23 to 27 mm and mild-to-moderate reduction for size 21 mm. Conclusions The Carpentier-Edwards supra-annular aortic porcine bioprosthesis continues to provide excellent freedom from structural valve deterioration and overall freedom from valve-related residual morbidity, mortality, and reoperation up to 18 years. Hemodynamic performance is satisfactory. The prosthesis remains recommended for patients older than 70 years and for patients 61 to 70 years of age, especially when comorbid risk factors are not anticipated to provide extended survival.

Effective verbalization of pain requires progressive cognitive development and acquisition of social communication skills. Use of self-report in pediatric pain assessment assumes children have acquired a capacity to understand and use common words to describe pain. The current investigation documented the language most commonly used by young children to describe pain and the age of onset of use of these words. Two complementary research methodologies were employed. Study 1 used the CHILDES database, an aggregated transcript database of multiple research studies examining spontaneous speech development across childhood. Transcripts of 14 randomly selected studies, yielding a total of 245 child participants ranging in age from 1 to 9 years, were searched for seven English primary pain word-stems: 'ache', 'boo-boo', 'hurt', 'ouch', 'ow', 'pain', and 'sore'. Study 2 surveyed 111 parents of children aged 3 to 6 years old concerning words the children commonly used for pain. Parents rated their children's frequency and age of first use of the seven pain word-stems. Both studies indicated that the most frequently used word-stems were 'hurt', 'ouch', and 'ow'. These words first emerged in children's vocabularies as early as 18 months of age. The word-stem 'pain' was used relatively infrequently and gradually emerged in children's vocabularies. The findings indicate that young children rely on a select number of words to describe pain, with these words appearing in children's vocabularies at an early age. These results have implications for developmentally appropriate pain assessment in young children.

Emergence d’une competence a communiquer sa douleur chez le bebe et l’enfantDans cet article, nous commencons par une breve discussion concernant la nature du langage de la douleur et des observations sur l’acquisition du langage de la douleur par les enfants. Les bebes et les jeunes enfants sans langage ne sont pas depourvus de toute capacite de signaler leur detresse. Mais l’acces au langage donne la possibilite d’une forme differente, plus sophistiquee de communication a propos de la douleur. L’article decrit les resultats d’un programme de recherche examinant l’usage spontane d’un langage de la douleur chez de jeunes enfants bien portants en conversation avec leurs parents et d’autres adultes dans leur cadre habituel de vie. Nous avons utilise en outre une large banque de donnees contenant les transcriptions d’un grand nombre d’interactions verbales entre enfants et adultes.

ObjectiveThe Artificial Valve Endocarditis Reduction Trial was stopped on January 21, 2000, due to a higher incidence of paraprosthetic leak in the St Jude Medical Silzone prosthesis compared with the conventional prosthesis. The Artificial Valve Endocarditis Reduction Trial investigators reported the 2-year results in 2002. This retrospective study assessed the influence on thromboembolism and paraprosthetic leak to 7 years.MethodsA total of 253 patients had 254 operations: 80 aortic valve replacements, 139 mitral valve replacements, and 35 multiple replacements with placement of Silzone prostheses. The mean age was 58.6 years (range 21–84 years, median age 59.8 years), and there were 126 women (49.8%) and 74 concomitant procedures (coronary artery bypass 28.9%).ResultsMajor paraprosthetic leak (repair, re-replacement, or mortality) occurred in 10 of the original procedures after 30 days (3 aortic valve replacements, 3 mitral valve replacements, 4 multiple replacements). Nine occurrences in 8 patients—5 early (≤2 years) and 4 late (>2 years)—were managed. Seven were managed with definitive re-replacement. One was an early nonoperative fatality. There was 1 late fatality after the second late paraprosthetic leak reoperation. One of the 10 procedures occurring after 2 years had mild to moderate aortic valve replacement paraprosthetic leak managed as an incidental re-replacement at the time of correction of supra valvular patch stenosis. One additional occurrence, in addition to the 8 patients (2years) intervals with re-replacement. Late managed events may be manifestations of earlier occurring paraprosthetic leak. Follow-up echocardiograms should meet standards of care, 6 to 12 months after surgery and at the slightest suspicion of dysfunction. There is no advanced continuing risk of the St Jude Medical Silzone prosthesis.